P1171: CNS RELAPSE OF DIFFUSE LARGE B-CELL LYMPHOMA. CLINICAL PRESENTATION, OUTCOME AND ROLE OF UPFRONT PROPHYLAXIS: A 10-YEAR SINGLE CENTER EXPERIENCE.
Authors: Corrado Benevolo Savelli, Mattia Novo, Filippo Fasano, Andrea Evangelista, Federica Cavallo, Carola Boccomini, Lorella Orsucci, Michele Clerico, Veronica Peri, Benedetto Bruno, Barbara Botto, Roberto Freilone
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma (DLBCL) represents the most frequent non-Hodgkin’s lymphoma, accounting alone for more than 60% of “aggressive” lymphomas. Central nervous system (CNS) recurrence is a rare event, occurring in about 5% of patients (pts) and correlating with a very dismal prognosis. By virtue of the anatomical localization therapeutic protocols possess limited efficacy, and, therefore, much debate has surrounded the use of a prophylactic strategy that would avert a priori CNS disease recurrence. CNS prophylaxis is mostly based on high-dose intravenous methotrexate (HD-MTX) although its effectiveness is controversial. Aims: Our study focuses on pts with CNS relapse of DLBCL by retrospectively analyzing cases diagnosed and treated at AOU Città della Salute e della Scienza di Torino (Turin), in order to evaluate their clinical and biological features, the validity of known prognostic scores, the efficacy of CNS prophylaxis, treatment at the time of relapse, and their prognosis. Methods: All pts with DLBCL diagnosed between January 1, 2010 and December 31, 2021 and treated with curative intent were retrospectively selected. A total of 498 cases with at least 12 months of follow-up were identified. Pts treated without curative intent or with primary mediastinal lymphoma, primary testicular lymphoma or CNS disease at diagnosis were excluded from the subsequent analysis. Results: The remaining case series included 406 pts. Mean age of the whole population was 67 years, 56/400 had ECOG PS ≥ 2 (14%), 231/400 elevated serum LDH levels (58%), 251/404 were stage IV (62%), 192/374 IPI score ≥ 3 (51%), 189/373 CNS-IPI 2-3 (51%), 91/373 CNS-IPI 4-6 (24%). Ninety-five out of 397 pts received CNS prophylaxis (24%): 59 by intrathecal (IT) route only (15%), 25 by intravenous MTX only (6%) (17 HD-MTX ≥3 g/mq), and 11 by combined route (3%). Twelve pts experienced CNS relapse; 8 of them exclusively CNS and 4 in synchrony with systemic recurrence. The cumulative incidence at 3 years was 2.8%. In univariate analysis, the CNS relapse risk was significantly influenced by ECOG PS and elevated serum LDH levels, while the use of prophylaxis was not shown to impact the risk of CNS recurrence. However none of the pts treated upfront with systemic MTX prophylaxis had subsequent CNS disease while 2/59 pts who received exclusive IT prophylaxis had CNS relapse with a superimposable incidence of the whole cohort (3.3%). In multivariate analysis, only ECOG PS confirmed significant correlation with the risk of such disease recurrence (figure 1). With a mean follow-up of 36 months, the 3-year progression free survival (PFS) and overall survival (OS) for the whole cohort were 69% and 77%, respectively; the 3-year OS for pts with SNC recurrence was 30% with no significant differences compared with pts with other relapse sites. Summary/Conclusion: Data from our case series confirm the limited benefit of IT prophylaxis. Although a statistically significant benefit from the use of HD-MTX prophylaxis is not shown in our series, probably due to the limited sample size and the number of overall events, the abandonment of this therapeutic strategy is not justified. The results of univariate and multivariate regression analyses agree in reporting that the CNS-IPI score is not always a reliable parameter. CNS recurrence of DLBCL continues to be a major challenge in oncohematology and the identification of new predicting factors of CNS relapse may help in intensifying and directing prophylactic strategies on a more selected very high-risk population.Figure 1. Multiple regression model for incidence of CNS relapse; cumulative incidence of CNS relapse by ECOG PS and by CNS-IPI score. Keywords: CNS lymphoma, Prophylaxis, Diffuse large B cell lymphoma, relapsed/refractory